Immune mechanisms in the induction of EAE have been studied in two species: Str 13 guinea pigs and outbred rabbits. a) Chronic (demyelinating) EAE can be induced in Str 13 guinea pigs by a combination of BP-sensitized cell transfer and sensitization of the recipients with whole CNS tissue (guinea pig cord). Chicken brain (which is non-encephalitogenic) can be substituted for guinea pig cord (which contains encephalitogenic BP). Fractionation of the former to identify the "antigen" responsible for inducing demyelination has indicated localization of the "antigen" in myelin. Further fractionation has been unsuccessful. (b) The specificity of the rabbit encephalitogenic site has been investigated with purified proteolytic fragments of BP. The first site reported to be active was located in peptic fragment 45-87. We and others noted that Res 1-44 were also active. We have further localized that site to Res 15-31, with overlapping peptides. Most assays of individual fragments failed to elicit 100% response in a group of rabbits. We questioned whether this was caused by genetic differences in the individual rabbits. Eighteen rabbits were sensitized with whole BP and the proliferative response of their lymph node cells was tested. Some rabbits responded only to Fragment 45-87; some to both (45-87) and (1-44). In general, response to both BP and fragments was higher when clinical signs of EAE were positive. The site in Fragment 45-87 appeared to be the most active.